Taken together, our results establish pten+/- mice as an excellent animal model system for the investigation of PTEN-related hamartoma syndromes, as well as the role of PTEN in breast and endometrial carcinogenesis.
PI(3)K-mediated activation of the cell survival kinase PKB/Akt, and negative regulation of PI(3)K signalling by the tumour suppressor PTEN (refs 3, 4) are key regulatory events in tumorigenesis.
These results strongly support PTEN as a major tumor suppressor on 10q involved in melanoma tumorigenesis and suggest an epigenetic mechanism of biallelic functional inactivation not previously observed in other cancers where PTEN might be involved.
However, somatic mutations of PTEN may not play a major role in tumorigenesis, at least in colorectal cancers, esophageal papillomas and gingival papillomas.
To investigate the potential role of the PTEN gene in renal tumorigenesis, we searched for abnormalities of the gene in 68 primary renal-cell carcinomas (RCCs) as well as in 17 renal carcinoma-derived cell lines, using DNA-SSCP, sequencing and microsatellite analysis.
To investigate the potential role of the PTEN gene in the carcinogenesis of ovarian endometrioid carcinoma and its related subtype, clear cell carcinoma, we examined 20 ovarian endometrioid carcinomas, 24 clear cell carcinomas, and 34 solitary endometrial cysts of the ovary for LOH at 10q23.3 and point mutations within the entire coding region of the PTEN gene.
The presence of PTEN mutations in hyperplasia suggests that PTEN inactivation may occur as an initiating event in endometrial carcinogenesis and is involved in the development of cytologic atypia in hyperplasia.
To study the possible role of PTEN in MCC oncogenesis, loss of heterozygosity (LOH) analysis for the 10q23 region was performed on 26 MCC tumor samples from 23 MCC patients.
Further studies will disclose a better understanding of the role of mutation in the PTEN gene in the course of tumorigenesis of both benign and malignant tumors developed in patients with CD.
Alternatively, these observations could also suggest that pathways involving other than Akt, p27 and cyclin D1 that lie downstream of PTEN play roles in ovarian carcinogenesis.
Enhanced tumor growth caused by constitutive activation of Akt in PTEN(+/+) cells also was reversed by CCI-779 treatment, indicating that FRAP/mTOR functions downstream of Akt in tumorigenesis.
This report reveals, by using CGH, that most MI+ endometrial cancers with PTEN/MMAC1 mutations as well as MI- tumors showed inactivation of both alleles of this gene, which strongly suggested the involvement of this gene in carcinogenesis.
These patients presented with advanced or metastatic CRC CONCLUSIONS: Overall, these results show that PTEN alteration together with TGF-beta pathway inactivation could contribute to tumorigenesis and metastatic spread of sporadic and microsatellite unstable CRC.
These results suggest that PTEN plays a significant pathogenic role in both HNPCC and sporadic endometrial carcinogenesis, unlike the scenarios for colorectal cancer.
Thus, unlike the p16 and p15 tumor suppressor genes, which are frequently deleted and inactivated in brain lymphoma and represent a striking contrast to systemic lymphoma, MMAC1 may not play an important role in carcinogenesis in this tumor, as in the systemic counterpart.
Since little is known about the molecular pathobiology, our goal was to investigate the potential role of the PTEN gene in the carcinogenesis of uterine sarcomas.
To elucidate the role of p53/p16(INK4a)/RB1 pathways in prostate carcinogenesis, we analyzed the p14(ARF), p16(INK4a), RB1, p21(Waf1), p27(Kip1), PTEN, p73, p53, and MDM2 gene status of multiple areas within 16 histologically heterogeneous prostate carcinomas using methylation-specific polymerase chain reaction, differential polymerase chain reaction, and immunohistochemistry.
In order to assess the role of PTEN in gastric carcinogenesis, we analysed the expression of PTEN in human gastric cancer and in the gastric mucosa of cancer relatives.